Abstract
One-electron reduction of the aromatic nitro-containing drug, clonazepam, by rat hepatic microsomes was found to produce a nitro anion radical which was observable by electron paramagnetic resonance (EPR) spectrometry under anaerobic conditions. It was determined that NADPH-cytochrome P-450 reductase may be the enzyme responsible for this reduction and that this free radical reacts rapidly with oxygen to produce Superoxide. The vasodilator nifedipine, another aromatic nitro-containing drug, was found not to be reduced by rat hepatic microsomes to a free radical nor to stimulate Superoxide production. Based on a series of experiments, we propose that the inability of nifedipine to be bioreduced to its nitro anion free radical is the result of geometric restrictions which prevent the transfer of an electron from cytochrome P-450 reductase to nifedipine.
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